Polyproline and triple helix motifs in host-pathogen recognition

Abstract

Secondary structure elements often mediate protein-protein interactions. Despite their low abundance in folded proteins, polyproline II (PPII) and its variant, the triple helix, are frequently involved in protein-protein interactions, likely due to their peculiar propensity to be solvent-exposed. We here review the role of PPII and triple helix in mediating hostpathogen interactions, with a particular emphasis to the structural aspects of these processes. After a brief description of the basic structural features of these elements, examples of host-pathogen interactions involving these motifs are illustrated. Literature data suggest that the role played by PPII motif in these processes is twofold. Indeed, PPII regions may directly mediate interactions between proteins of the host and the pathogen. Alternatively, PPII may act as structural spacers needed for the correct positioning of the elements needed for adhesion and infectivity. Recent investigations have highlighted that collagen triple helix is also a common target for bacterial adhesins. Although structural data on complexes between adhesins and collagen models are rather limited, experimental and theoretical studies have unveiled some interesting clues of the recognition process. Interestingly, very recent data show that not only is the triple helix used by pathogens as a target in the host-pathogen interaction but it may also act as a bait in these processes since bacterial proteins containing triple helix regions have been shown to interact with host proteins. As both PPII and triple helix expose several main chain non-satisfied hydrogen bond acceptors and donors, both elements are highly solvated. The preservation of the solvation state of both PPII and triple helix upon protein-protein interaction is an emerging aspect that will be here thoroughly discussed.

Fig. (1)

Representation of the interaction between the α-helix (light grey) and the PPII helix (dark grey) found in AgI/II structure (PDB code 3iox). For clarity, the PPII helix was reported as a stick model.

Fig. (2)

Scheme ‘collagen acts as a target and a bait’.

Fig. (3)

Crystal structures of complexes between proteins and collagen triple helices. Left panel reports sequences of bound triple helices: residues of the triple helices located within 4 Å from the receptor are reported in grey boxes. Right panels report ribbon representations of their three-dimensional structures. Panels A-G refer to complexes of triple helices with integrin alpha 2 I domain (PDB code 1dzi), CNA (2f6a), SPARC (2v53), DDR2 discoidin domain (2wuh), MASP-1 CUB2 domain (3pob), Von Willebrand factor A3 domain (4dmu), matrix metalloproteinase 1 (4auo), and the chaperone Hsp47/SERPINH1 (4awr) respectively.

Fig. (4)

(A) domain organisation of MSCRAMM proteins CNA and ACE: The N-terminal signal peptide (SP) is followed by A and B regions, the C-terminal cell wall sorting region W, the transmembrane region M and the cytoplasmatic tail C. (B) CNA structure in complex with the collagen triple helix. The N1 and N2 domains of the A region are shown in light and dark gray, respectively. Collagen triple helix (black) is wrapped by the linker region between N1 and N2, represented in ball-and-stick.

Fig. (5)

Collagen hug mechanism. (A), CNA open and close forms exist in equilibrium; (B) Collagen binds to the N2 domain; (C) collagen is wrapped by N1 and N2 domains and by the inter-domain linker.

Fig. (6)

Domain organization of Scl proteins main features are: an N-terminal globular (V) domain, a collagen-like (CL) domain, and a C-terminal Gram-positive cell wall attachment domain (Gram+ anchor).